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Journal of Biomedical Optics • Open Access

Gentamicin differentially alters cellular metabolism of cochlear hair cells as revealed by NAD(P)H fluorescence lifetime imaging
Author(s): Lyandysha V. Zholudeva; Kristina G. Ward; Michael G. Nichols; Heather Jensen Smith

Paper Abstract

Aminoglycoside antibiotics are implicated as culprits of hearing loss in more than 120,000 individuals annually. Research has shown that the sensory cells, but not supporting cells, of the cochlea are readily damaged and/or lost after use of such antibiotics. High-frequency outer hair cells (OHCs) show a greater sensitivity to antibiotics than high- and low-frequency inner hair cells (IHCs). We hypothesize that variations in mitochondrial metabolism account for differences in susceptibility. Fluorescence lifetime microscopy was used to quantify changes in NAD(P)H in sensory and supporting cells from explanted murine cochleae exposed to mitochondrial uncouplers, inhibitors, and an ototoxic antibiotic, gentamicin (GM). Changes in metabolic state resulted in a redistribution of NAD(P)H between subcellular fluorescence lifetime pools. Supporting cells had a significantly longer lifetime than sensory cells. Pretreatment with GM increased NAD(P)H intensity in high-frequency sensory cells, as well as the NAD(P)H lifetime within IHCs. GM specifically increased NAD(P)H concentration in high-frequency OHCs, but not in IHCs or pillar cells. Variations in NAD(P)H intensity in response to mitochondrial toxins and GM were greatest in high-frequency OHCs. These results demonstrate that GM rapidly alters mitochondrial metabolism, differentially modulates cell metabolism, and provides evidence that GM-induced changes in metabolism are significant and greatest in high-frequency OHCs.

Paper Details

Date Published: 17 February 2015
PDF: 12 pages
J. Biomed. Opt. 20(5) 051032 doi: 10.1117/1.JBO.20.5.051032
Published in: Journal of Biomedical Optics Volume 20, Issue 5
Show Author Affiliations
Lyandysha V. Zholudeva, Drexel Univ. College of Medicine (United States)
Kristina G. Ward, Creighton Univ. (United States)
Michael G. Nichols, Creighton Univ. (United States)
Heather Jensen Smith, Creighton Univ. (United States)

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